PAI-1, Obesity, Insulin Resistance and Risk of Cardiovascular Events

Circulating (PAI-1) levels are elevated in patients with coronary heart disease and may play an important role in the development of atherothrombosis. Many clinical studies have indicated that the insulin resistance syndrome, which is a situation predisposing to diabetes and ischemic heart disease, may be a major regulator of PAI-1 expression, especially in determining plasma PAI-1 levels. Central obesity is a characteristic of insulin resistance and is a well recognized risk factor for coronary heart disease. Recently the production of PAI-1 by adipose tissue, in particular by tissue from omentum, has been demonstrated and could be an important contributor to the elevated plasma PAI-1 levels observed in insulin resistant patients. Besides the effect of the metabolic status on plasma PAI-1 levels, the role of a genetic control has been emphasized, but according to recent results obtained in a family segregation study, its participation seems limited. Prospective cohort studies of patients with previous myocardial infarction or angina pectoris have underlined the association between increased plasma PAI-1 levels and the risk of coronary events, but the predictive capacity of PAI-1 disappears after insulin resistance marker adjustments. Taken together these results support the notion that PAI-1 can be a link between obesity, insulin resistance and cardiovascular disease.